Technical Abstract:
Damage to the intestinal epithelium reduces nutrient absorption and animal growth, and can have negative long-term health effects on livestock. The intestinotropic hormone glucagon-like peptide 2 (GLP-2) contributes to gut integrity, reduces inflammation, and improves nutrient absorption. The present study was designed to determine whether GLP-2 administration to calves with coccidiosis in the first month of life affects intestinal growth and mediates negative impacts of the proinflammatory response. Holstein bull calves (n = 19) were assigned to 4 treatment groups of 4 to 5 calves each: 1) infected with Eimeria bovis, GLP-2-treated; non-infected, GLP-2-treated; 3) infected with E. bovis, buffer-treated; and 4) non-infected, buffer-treated. On d 0, infected calves received 100,000 to 200,000 sporulated E. bovis oocysts suspended in milk replacer. On d 18, calves in the GLP-2 groups received a subcutaneous injection of 50 µg/kg BW of bovine GLP-2 twice daily for 10 d, and calves in the buffer-treated groups received an equivalent volume of buffer. On d 28, calves were euthanized 2 h after injection of 5-bromo-2'-deoxyuridine (BrdU). Intestinal tissues were measured and villus height, crypt depth, and BrdU immunostaining were evaluated in segments of the small intestine. Nitrotyrosine immunostaining, a measure of nitro-oxidative damage, was evaluated in ileum and cecum. There was a GLP-2 treatment by E. bovis infection interaction only for nitrotyrosine immunostaining in cecum (P = 0.005). Large intestinal weight was greater (P = 0.03) in infected than non-infected calves and with GLP-2 treatment relative to buffer treatment. Calves that received GLP-2 had greater (P = 0.01) small intestinal weight relative to buffer-treated calves, but an increase in cell proliferation was detected only in jejunum (P = 0.08), as assessed by BrdU labeling. No treatment effects were detected (P = 0.12) for villus height, crypt depth, or villus height:crypt depth ratio in segments of the small intestine. Protein tyrosine nitration was over 3-fold greater (P = 0.004) in ileum and cecum of infected calves relative to non-infected calves, and GLP-2 therapy reduced tyrosine nitration in infected calves by 47% in ileum (P < 0.05) and 69% in cecum (P < 0.0001) relative to buffer-treated calves. Thus, GLP-2 promotes intestinal growth in neonatal calves and GLP-2 therapy reduces the detrimental effects of nitro-oxidative stress in ileocecum of calves with coccidiosis.